Although there are great differences in the morbidity and mortality of colorectal cancer all over the world, in most developed countries, colorectal cancer is always the third cause of cancer-related death. The monoclonal antibodies targeting Epidermal Growth Factor Receptor (EGFR), such as cetuximab, panitumumab, can significantly improve the survivals of patients in the treatments of patients with RAS wild-type metastatic colorectal cancers (mCRCs), thus they are recommended for the treatments of RAS wild-type mCRCs. Currently, although RAS gene detection has been used as a conventional detection of selecting EGFR monoclonal antibodies for the patients, the treatments of EGFR monoclonal antibodies are ineffective for 30-40% of RAS wild-type patients. More importantly, the majority of RAS wild-type patients will still develop drug resistance after receiving the treatments of EGFR monoclonal antibodies. Therefore, it is of great significance for the instruction of the clinic applications of EGFR monoclonal antibodies to timely monitor the occurrence of drug resistance before the treatment is confirmed as ineffective by imageology, so as to avoid unnecessarily prolonged ineffective treatment.
Recent studies reported that a series of genes downstream of EGFR signal pathway, such as BRAF, PIK3CA and PTEN, may relate to the drug resistance of EGFR monoclonal antibodies. However, several studies obtained contradictory conclusions, and in the studies related to drug resistance, the traditional method is to focus on the somatic mutations which have existed in tumor tissues before the treatments, and to monitor their changes during the process of treatments, but such strategy may ignore new mutations occurring during the process of treatments, resulting in being unable to sufficiently assess the gene mutations related to drug resistance.